Heterozygous NTF4 mutations impairing neurotrophin-4 signaling in patients with primary open-angle glaucoma

Pasutto, F. and Matsumoto, T. and Mardin, C. Y. and Sticht, H. and Brandstatter, J. H. and Michels-Rautenstrauss, K. and Weisschuh, N. and Gramer, E. and Ramdas, W. D. and van Koolwijk, L. M. E. and Klaver, C. C. W. and Vingerling, J. R. and Weber, B. H. F. and Kruse, F. E. and Rautenstrauss, B. and Barde, Y. -A. and Reis, A.. (2009) Heterozygous NTF4 mutations impairing neurotrophin-4 signaling in patients with primary open-angle glaucoma. American journal of human genetics, Vol. 85, H. 4. pp. 447-456.

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Official URL: http://edoc.unibas.ch/dok/A5259496

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Glaucoma, a main cause of blindness in the developed world, is characterized by progressive degeneration of retinal ganglion cells (RGCs), resulting in irreversible loss of vision. Although members of the neurotrophin gene family in various species are known to support the survival of numerous neuronal populations, including RGCs, it is less clear whether they are also required for survival and maintenance of adult neurons in humans. Here, we report seven different heterozygous mutations in the Neurotrophin-4 (NTF4) gene accounting for about 1.7% of primary open-angle glaucoma patients of European origin. Molecular modeling predicted a decreased affinity of neurotrophin 4 protein (NT-4) mutants with its specific tyrosine kinase receptor B (TrkB). Expression of recombinant NT-4 carrying the most frequent mutation was demonstrated to lead to decreased activation of TrkB. These findings suggest a pathway in the pathophysiology of glaucoma through loss of neurotrophic function and may eventually open the possibility of using ligands activating TrkB to prevent the progression of the disease.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Pharmacology/Neurobiology (Barde)
UniBasel Contributors:Barde, Yves-Alain
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Univ. of Chicago Press
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:22
Deposited On:22 Mar 2012 13:28

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